Field of the Invention
The invention relates to anthracycline glycosides having antitumour properties, to processes for their preparation, and to pharmaceutical compositions containing them.
The invention provides 4'-deoxy-3'-epi-daunorubicin, 4'-deoxy-3'-epi-doxorubicin and their pharmaceutically acceptable salts.
4'-deoxy-3'-epi-daunorubicin and 4'-deoxy-3'-epi-doxorubicin have the following formula A: ##STR1## R representing a hydrogen atom and a hydroxy group respectively.
The invention further provides a process for the preparation of 4'-deoxy-3'-epi-daunorubicin, which process comprises reducing 3'-epi-4'-keto-N-trifluoroacetyl-daunorubicin (I) with sodium borohydride to obtain a mixture of axial II and equatorial III, 4' hydroxy derivatives replacing the 4'-hydroxy group of either of both thereof by an iodine atom by treatment with trifluoromethane-sulphonic anhydride in the presence of an organic base followed by treatment with an excess of tetrabutylammonium iodide, reductively dehalogenating the resultant 4'-iodo derivatives IV and V by treatment with tributyltin hydride in the presence of N,N'-azobis (isobutyronitrile), and removing the N-trifluoroacetyl group from the resultant 3'-epi-4'-deoxy-N-trifluoroacetyl-daunorubicin (VI) by mild alkaline hydrolysis.
The process is illustrated by the following reaction scheme, to which the compound numbers included in the last preceding paragraph refer. In the reaction scheme, D represents the group ##STR2## Me represents a methyl group and TFA represents a trifluoroacetyl group.